Immunologic Effects of Omalizumab in Children with Severe Refractory Atopic Dermatitis: A Randomized, Placebo-Controlled Clinical Trial

Abstract

Background: Severe refractory atopic dermatitis (AD) is a chronic, debilitating condition that is associated with elevated serum immunoglobulin E (IgE) levels. Thymic stromal lymphopoietin (TSLP), thymus and activation-regulated chemokine (TARC) and OX40 ligand (OX40L) are important immunologic factors involved in the pathogenesis of AD. Omalizumab, an anti-IgE antibody indicated for use in allergic asthma, is implicated in regulating allergen presentation by dendritic cells and the T cell response during the effector phases of allergic disease. We investigated if anti-IgE therapy modulates the allergen-specific responses mediated by the TSLP pathway in young patients with severe refractory AD. Methods: This was a randomized, double-blind, placebo-controlled study of 8 patients between the ages of 4 and 22 years (mean = 11.6 years) with severe refractory AD (clinical trials.gov NCT01678092). Serum IgE ranged from 218 to 1,890 (mean = 1,068 IU/ml). Subjects received omalizumab (n = 4) or placebo (n = 4) every 2-4 weeks over 24 weeks using a regimen extrapolated from the package insert. TSLP, TARC, OX40L and other cytokines involved in AD were measured by using cytometric bead arrays. Results: All patients receiving omalizumab had strikingly decreased levels of TSLP, OX40L, TARC (involved in Th2 polarization) and interleukin (IL)-9 compared to placebo. In addition, there was a marked increase in IL-10, a tolerogenic cytokine, in the omalizumab-treated group. Patients on anti-IgE therapy had an improvement in clinical outcomes as measured by the SCORAD system; however, these effects were comparable to improvements in the control group. Conclusions: Anti-IgE therapy with omalizumab decreases levels of cytokines that are involved in Th2 polarization and allergic inflammation, including TSLP, TARC and OX40L.

Omalizumab (Xolair) in Children with Atopic Dermatitis: A Review Article

“…It seems that Xolair could be effective in decreasing IgE levels in different doses and durations of the treatment, although, the decrease of IgE level is not important on its own. Some studies showed that the decrease of IgE did not associate with clinical resolutions (9,11). Clinical manifestations improved in all of the studies (3,(8)(9)(10)(11)(12)(13)(14) except one, other researches had no control group.…”

“…Serum IgE level was increased in all patients. Only one of those studies included a control group (11). AD were associated with other allergic disorders such as asthma and allergic rhinitis (AR) in all patients (Table 1).…”

“…AD were associated with other allergic disorders such as asthma and allergic rhinitis (AR) in all patients (Table 1). All patients had taken Xolair subcutaneously (SC) (3,(8)(9)(10)(11)(12)(13)(14).…”

“…Cases had taken the drug for 2 or 4 weeks SC. The drug dosage was different in these studies, from 150 mg, 150 mg to 375 mg, 225 mg to 375 mg, and 300 mg to 375 mg (9,(11)(12)(13). The reason for this difference is because of the difference in weight of the patients and baseline IgE.…”

“…It seems that the dose of the drug could be adjusted based on the patient's response. The duration of treatment was different from 12 weeks, 20 weeks, 24 weeks, and 12 to 67 months (9,(11)(12)(13). Serum IgE level decreased in 100% of the studies (3,(8)(9)(10)(11)(12)(13)(14).…”